Submissions for variant NM_001376.5(DYNC1H1):c.5985C>T (p.Ala1995=) (rs140841480)

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory,University of Chicago	RCV000194990	SCV000247214	benign	not specified	2017-05-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000194990	SCV000512899	likely benign	not specified	2017-12-13	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV001083329	SCV000559813	benign	Charcot-Marie-Tooth disease, axonal, type 2O	2019-12-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000720802	SCV000851686	likely benign	History of neurodevelopmental disorder	2017-05-22	criteria provided, single submitter	clinical testing	Synonymous alterations with insufficient evidence to classify as benign
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768205	SCV000898656	uncertain significance	Spinal muscular atrophy, lower extremity predominant 1, autosomal dominant; Charcot-Marie-Tooth disease, axonal, type 2O; Mental retardation, autosomal dominant 13	2017-10-23	criteria provided, single submitter	clinical testing	DYNC1H1 NM_001376.4 exon 30 p.Ala1995= (c.5985C>T): This variant has not been reported in the literature but is present in 103/126648 European alleles, including 1 homozygote in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs140841480). This variant is present in ClinVar (Variation ID:210873). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant is a silent variant and does not change the amino acid, reducing the probability that this variant is disease causing. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000470101	SCV001149332	uncertain significance	not provided	2016-04-01	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV001083329	SCV001267953	likely benign	Charcot-Marie-Tooth disease, axonal, type 2O	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Clinical Services Laboratory,Illumina	RCV001110505	SCV001267954	likely benign	Spinocerebellar Ataxia, Dominant	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001172871	SCV001335944	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing